Duo photoprotective effect via silica-coated zinc oxide nanoparticles and Vitamin C nanovesicles composites.

OBJECTIVE: Zinc Oxide nanoparticles (ZnO NPs) are used widely in nowadays personal care products, especially sunscreens, as a protector against UV irradiation. Yet, they have some reports of potential toxicity. Silica is widely used to cage ZnO NPs to reduce their potential toxicity. Vitamin C derivative, Magnesium Ascorpyl Phosphate (MAP), is a potent antioxidant that can efficiently protect human skin from harmful impacts of UV irradiation and oxidative stress. The combination of silica coated ZnO NPs and MAP nanovesicles could have potential synergistic protective effect against skin photodamage. METHODS: Silica coated ZnO NPs and MAP nanovesicles (ethosomes and niosomes) were synthesized, formulated, and evaluated as topical gels. These gel formulations were evaluated in mice for their photoprotective effect against UV irradiation through histopathology and immuno-histochemistry study. Split-face clinical study was conducted to compare the effect of application of silica coated ZnO NPs either alone or combined with MAP nanovesicles. Their photoprotective action was evaluated, using Antera 3D® camera, for melanin level, roughness index and wrinkles depth. RESULTS: Silica coated ZnO NPs when combined with MAP nanovesicles protected mice skin from UV irradiation and decreased the expression of the proinflammatory cytokines, NF-κB. Clinically, silica coated ZnO NPs, alone or combined with MAP nanovesicles, could have significant effect to decrease melanin level, roughness index and wrinkles depth with higher effect for the combination. CONCLUSION: A composite of silica coated ZnO NPs and MAP nanovesicles could be a promising cosmetic formulation for skin protection against photodamage signs such as hyperpigmentation, roughness, and wrinkles.

Fluorinated indeno-quinoxaline bearing thiazole moieties as hypoglycaemic agents targeting α-amylase, and α-glucosidase: synthesis, molecular docking, and ADMET studies.

Inhibition of α-glucosidase and α-amylase are key tactics for managing blood glucose levels. Currently, stronger, and more accessible inhibitors are needed to treat diabetes. Indeno[1,2-b] quinoxalines-carrying thiazole hybrids 1-17 were created and described using NMR. All analogues were tested for hypoglycaemic effect against STZ-induced diabetes in mice. Compounds 4, 6, 8, and 16 were the most potent among the synthesised analogues. These hybrids were examined for their effects on plasma insulin, urea, creatinine, GSH, MDA, ALT, AST, and total cholesterol. Moreover, these compounds were tested against α-glucosidase and α-amylase enzymes in vitro. The four hybrids 4, 6, 8, and 16 represented moderate to potent activity with IC50 values 0.982 ± 0.04, to 10.19 ± 0.21 for α-glucosidase inhibition and 17.58 ± 0.74 to 121.6 ± 5.14 µM for α-amylase inhibition when compared to the standard medication acarbose with IC50=0.316 ± 0.02 µM for α-glucosidase inhibition and 31.56 ± 1.33 µM for α-amylase inhibition. Docking studies as well as in silico ADMT were done.

The neuroprotective potential of curcumin on T. Spiralis infected mice.

BACKGROUND: Trichinella spiralis can affect the brain by inducing inflammatory and vascular changes. Drug management with the antiparasitic drug albendazole can be enhanced by natural compounds such as curcumin. The potential benefit of curcumin as an adjuvant to albendazole in the management of cerebral affection during experimental T. spiralis infection was evaluated. Animals received either curcumin 150 mg/Kg, albendazole 50 mg/Kg or a combination of both drugs. Animal groups receiving treatment were compared with infected and non-infected control groups. Blood levels of reduced glutathione (GSH) and dopamine were measured, and brain tissue expression of cyclooxygenase-2 enzyme (COX-2) and CD34 was assessed by immunohistochemistry. RESULTS: T. spiralis infection resulted in a state of oxidative stress, which was improved by albendazole and curcumin. Also, both drugs restored the peripheral dopamine level, which was decreased in infected non-treated mice. Curcumin was also found to be efficient in improving brain pathology and reducing local COX-2 and CD 34 expression. CONCLUSIONS: Inflammatory and pathological changes during neurotrichinosis can be improved by the addition of curcumin to conventional anti-parasitic drugs.

Insight into the hepatoprotective, hypolipidemic, and antidiabetic impacts of aliskiren in streptozotocin-induced diabetic liver disease in mice.

BACKGROUND: Diabetic hepatopathy is a serious complication of poorly controlled diabetes mellitus. An efficient antidiabetic drug which keeps normal liver tissues is not available. The renin-angiotensin system has been reported to be involved in both diabetic state and liver function. Aliskiren is a direct renin inhibitor and a recently antihypertensive drug with poly-pharmacological properties. The aim of the current study is to explore the possible hepatoprotective effects and mechanisms of action of aliskiren against streptozotocin (STZ) induced liver toxicity. METHODS: Mice were distributed to 3 groups; first: the normal control group, second: the diabetic control group, third: the diabetic group which received aliskiren (25 mg/kg; oral) for 4 weeks. At the end of the treatment period, plasma glucose, insulin, lipid profile, oxidative stress, and liver function tests were evaluated spectrophotometrically. ELISA technique was used to measure the expression levels of TNF-α and adiponectin. Furthermore, a Histopathological examination of liver samples was done. RESULTS: It was shown that aliskiren treatment ameliorated the STZ-induced oxidative stress and elevated inflammatory biomarkers, hypercholesterolemia, serum aminotransferases and alkaline phosphatase levels in diabetic mice. In addition, hepatocellular necrosis, and fibrosis were improved by aliskiren treatment. CONCLUSION: aliskiren protects against the liver damage caused by STZ-induced diabetes. This can be explained by its ability to block angiotensin-II, and its anti-diabetic, hypocholesterolemic, antioxidant and anti-inflammatory effects. Aliskiren could be a novel therapeutic strategy to prevent liver diseases associated with hypertension and diabetes mellitus.

Investigation of the impacts of zamzam water on streptozotocin-induced diabetic nephropathy in rats. In-vivo and in-vitro study.

BACKGROUND: Oxidative stress is considered the main event in the pathogenesis. of diabetic nephropathy (DN). Zamzam water, being natural alkaline with exceptional characteristics, is capable of enhancing antioxidant mechanisms. In this context; the present study has aimed to investigate the protective effects of zamzam water alone or in combination with gliclazide against the streptozotocin (STZ) induced DN model in rats. METHODS: DN was initiated by a single intraperitoneal dose of STZ. Three days later, diabetic rats were classified into 5 groups; a normal control group, a diabetic control group, a group receiving gliclazide, a group receiving zamzam water, and a group receiving both gliclazide and zamzam water. Blood pressure (BP) and heart rate (HR) were determined. Then rats were euthanized and serum was isolated for assessment of glucose, insulin, kidney function tests and nitric oxide (NO). Furthermore kidney contents of malondialdehyde (MDA) and reduced glutathione (GSH) were estimated. Histopathology or renal tissues and immunohistochemistry of caspase 3 were determined. In addition, islets of Langerhans were separated from normal rats by collagenase digestion method to study the effects of zamzam water on insulin release in-vitro. Furthermore, chemical analysis of zamzam water has been done. RESULTS: Zamzam water significantly decreased STZ-induced hyperglycemia, BP, HR, oxidative stress biomarkers, impairment in renal functions (urea, creatinine, albumin), morphological changes in kidney and apoptosis. Likewise, zamzam water markedly elevated insulin levels both in in-vivo and in in-vitro experiments. The effects were more pronounced in combination with gliclazide. CONCLUSION: Zamzam water has a promising renoprotective effect against STZ induced DN through its anti-diabetic, antioxidant, anti-inflammatory and anti-apoptotic potentials.

In Vivo Pharmacological Testing of Herbal Drugs for Anti-Allergic and Anti-Asthmatic Properties.

Background: Asthma is a chronic inflammatory disease characterized by reversible airway obstruction, hyperresponsiveness, and remodeling. Asthma prevalence has increased significantly globally over the last decade, and it remains incurable to this date. Aims and Objectives: The present study evaluated some of the antiasthmatic medicinal plants to assess their mode of action. Materials and Method: Animal models for milk-induced leukocytosis, milk-induced eosinophilia, mast cell degranulation, clonidine-induced catalepsy, and active paw anaphylaxis were used to assess the pharmacological effects of Ammi visnaga, Medicago sativa, and Urtica dioica. Results: Mice pretreated with diazepam, methanolic extract of M. sativa, and U. dioica exhibited significant (P < 0.05) inhibition in milk-induced leukocytosis. However, only M. sativa showed statistically significant (P < 0.05) results. All plants showed a statistically significant (P < 0.05) tendency to decrease milk-induced eosinophilia. Methanolic extracts of all plants significantly (P < 0.05) protected mast cells against degranulation by clonidine. A. visnaga and U. dioica significantly (P < 0.05) protected mice against clonidine-induced catalepsy. An acute treatment by M. sativa potentiated the catalepsy, while it significantly inhibited the catalepsy (P < 0.05) upon chronic treatment. In the allergic inflammation model, methanolic extracts of all plants under study decreased paw thickness in a statistically significant manner (P < 0.05). Conclusion: All the three plants in this study demonstrated anti-inflammatory and antihistaminic effects, as well as decreased paw thickness, validate anti-allergic properties. A. visnaga showed a mast cell-stabilizing effect. A. visnaga and U. dioica inhibited the histamine-mediated clonidine-induced catalepsy from mast cells which proves the antihistaminic activity of these plants.

Social behavior effects of diphenyl dimethyl bicarboxylate (DDB) in the sensory contact model.

Sensory contact model (SCM) permits the evolution of diverse psychopathological states by the repeated antagonistic interactions between male mice. Biphenyl dimethyl dicarboxylate (DDB) is used as a hepatoprotective agent. The present work aimed to study the possible effects of DDB on social behavior developed by SCM by studying its effects on the transformation process to aggressive and submissive behaviors. Besides, measuring behavioral changes using the open field test (OFT) and the elevated plus maze test (EPM), neurochemical parameters [serotonin (5HT), norepqinephrine (NE), and dopamine(DA)], and immunological changes (total leucocyte count, differential leucocytic count, and evaluation of bone marrow lymphocytes count and viability assessment). Adult male Swiss mice were used; DDB was given in a dose of 100 mg/kg by oral gavage daily for 2 weeks from the fifth day to the last day of the SCM. The present study concluded that administration of DDB to the SCM involved animals was shown to be associated with significant positive impacts on the behavior of depressed partner in the SCM which were manifested by decreased latency and increased ambulation and rearing in OFT, increased number of entry in the open arm/total no of entries in EPM. This was associated with changes in brain levels of neurotransmitters which were manifested by increased NE and decreased DA, as well as the examined immunity related parameters which were manifested by increased total leucocyte count, bone marrow lymphocytes, and monocytes. So DDB can be used as a supportive antidepressant agent in patients with liver impairment and should be avoided in aggressive ones. However, more randomized controlled trials should be carried out to ascertain these effects.

Neuroprotective effects of vitamin D alone or in combination with lamotrigine against lithium-pilocarpine model of status epilepticus in rats.

Status epilepticus (SE) is considered one of the major serious forms of epilepsy with high mortality rate. Since the currently available antiepileptic drugs have low efficacy and high adverse effects, new more efficient and safe therapies are critically needed. There is increasing evidence supporting dietary and alternative therapies for epilepsy, including the ketogenic diet, modified Atkins diet, and omega-3 fatty acids. Recent studies have shown significant prophylactic and therapeutic potential of vitamin D (vit-D) use in many neurological disorders. Therefore, in the present study, the neuroprotective effects and mechanisms of vit-D alone or in combination with lamotrigine have been evaluated in the lithium-pilocarpine model of SE in rats. Rats were divided into five groups: normal group, SE group, lamotrigine (25 mg/kg/day) pretreated group, vit-D (1.5 mcg/kg/day) pretreated group, and group pretreated with vit-D and lamotrigine for 2 weeks. At the end of treatment, SE was induced by single intraperitoneal injection of LiCl (127 mg/kg), followed 24 h later by pilocarpine (30 mg/kg). Seizures' latency, cognitive performance in Morris water maze, brain oxidative stress biomarkers (glutathione, lipid peroxides, and nitric oxide), brain neurochemistry (γ-aminobutyric acid and glutamate), and brain histopathology have been evaluated. Vit-D prevented pilocarpine-induced behavioral impairments and oxidative stress in the brain; these results were improved in combination with lamotrigine. Vit-D has a promising antiepileptic, neuroprotective, and antioxidant effects. It can be provided to patients as a supportive treatment besides antiepileptic drugs. However, clinical trials are needed to establish its efficacy and safety.

Anti-diabetic and renoprotective effects of aliskiren in streptozotocin-induced diabetic nephropathy in female rats.

Since chronic kidney disease due to diabetic nephropathy (DN) is becoming an ever larger health burden worldwide, more effective therapies are desperately needed. In the present study, the anti-diabetic and renoprotective effects of aliskiren have been evaluated in streptozotocin (STZ)-induced DN in rats. DN was induced by a single intraperitoneal injection of STZ (65 mg/kg). Three weeks after STZ, rats were divided into four groups; normal, diabetic, diabetic treated with gliclazide (10 mg/kg/day) for 1 month, and diabetic treated with aliskiren (50 mg/kg/day) for 1 month. At the end of the experiment, mean arterial blood pressure and heart rate were recorded. Rats were then euthanized and serum was separated for determination of glucose, insulin, kidney function tests, superoxide dismutase activity (SOD), adiponectin, and tumor necrosis factor-alpha (TNF-α). One kidney was used for estimation of malondialdehyde (MDA), reduced glutathione (GSH), and nitric oxide (NO) contents. Other kidney was used for histopathological study and immunohistochemical measurement of caspase-3 and transforming growth factor beta (TGF-ß). In addition, islets of Langerhans were isolated from normal rats by collagenase digestion technique for in vitro study. Aliskiren normalized STZ-induced hyperglycemia, increased insulin level both in vivo and in vitro, normalized kidney function tests and blood pressure, and alleviated STZ-induced kidney histopathological changes. This could be related to the ability of aliskiren toward preserving hemodynamic changes and alleviating oxidative stress and inflammatory and apoptotic markers induced by STZ in rats. However, aliskiren was more effective than gliclazide in relieving STZ-induced DN. These findings support the beneficial effect of aliskiren treatment in DN which could be attributed to its anti-diabetic, renoprotective, antioxidant, anti-inflammatory, and anti-apoptotic effects. Moreover, clinical studies are required to establish the effectiveness of aliskiren treatment in patients suffering from hypertension and diabetes.

The effect of some immunomodulatory and anti-inflammatory drugs on Li-pilocarpine-induced epileptic disorders in Wistar rats.

Evidence shows that inflammatory and immune processes within the brain might account for the pathophysiology of epilepsy. Therefore, developing new antiepileptic drugs that can modulate seizures through mechanisms other than traditional drugs is required for the treatment of refractory epilepsy. This study aims to determine the relationship between brain inflammation and epilepsy, to examine the contribution of some biochemical parameters involved in brain inflammation, and to address the effect of pharmacological interventions using some anti-inflammatory and immunomodulatory drugs in an experimental epilepsy model. Adult male rats were divided into seven groups of 20. G1 was the normal, non-treated control. G2 was the epileptic, non-treated group. G3-G7 were treated with celecoxib, methotrexate, azathioprine, dexamethasone, and valproate, respectively, for a period of three weeks. Induction of status epilepticus (SE) by Li-pilocarpine was performed on groups G2-G7. EEG tracing was conducted, and inflammatory mediators (brain and serum IL-1ß, IL 6, PGE2, HSP70, TGF-ß2, and IFNγ) were measured. The induction of SE increased the amplitude and frequency of EEG tracing and inflammatory mediators more than in the normal control group. Treatments of epileptic rats reduced the frequency and amplitude of EEG tracing and significantly decreased the levels of inflammatory mediators in some treated rats compared to G2. These findings demonstrate that some anti-inflammatory and immunomodulatory drugs can lower the frequency and amplitude of seizures and reduce some inflammatory mediators in epilepsy treatments, strengthening the possibility that targeting these immunological and inflammatory pathways may represent another effective therapeutic approach to preventing epileptic seizures.